Abstract

Characterising the hierarchy of mammary epithelial cells (MECs) and how they are regulated during adult development is important for understanding how breast cancer arises. Here we report the use of single-cell RNA sequencing to determine the gene expression profile of MECs across four developmental stages; nulliparous, mid gestation, lactation and post involution. Our analysis of 23,184 cells identifies 15 clusters, few of which could be fully characterised by a single marker gene. We argue instead that the epithelial cells—especially in the luminal compartment—should rather be conceptualised as being part of a continuous spectrum of differentiation. Furthermore, our data support the existence of a common luminal progenitor cell giving rise to intermediate, restricted alveolar and hormone-sensing progenitors. This luminal progenitor compartment undergoes transcriptional changes in response to a full pregnancy, lactation and involution. In summary, our results provide a global, unbiased view of adult mammary gland development.

Details

Title
Differentiation dynamics of mammary epithelial cells revealed by single-cell RNA sequencing
Author
Bach, Karsten 1 ; Pensa, Sara 2 ; Grzelak, Marta 3 ; Hadfield, James 3   VIAFID ORCID Logo  ; Adams, David J 4 ; Marioni, John C 5 ; Khaled, Walid T 2 

1  Department of Pharmacology, University of Cambridge, Cambridge, UK; Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK; Cancer Research UK Cambridge Cancer Centre, Cambridge, UK 
2  Department of Pharmacology, University of Cambridge, Cambridge, UK; Cancer Research UK Cambridge Cancer Centre, Cambridge, UK 
3  Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK; Cancer Research UK Cambridge Cancer Centre, Cambridge, UK 
4  Cancer Research UK Cambridge Cancer Centre, Cambridge, UK; Wellcome Trust Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK 
5  Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK; Cancer Research UK Cambridge Cancer Centre, Cambridge, UK; Wellcome Trust Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK; European Bioinformatics Institute, European Molecular Biology Laboratory, Hinxton, UK 
Pages
1-11
Publication year
2017
Publication date
Dec 2017
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41467-017-02001-5
ProQuest document ID
1983429703
Copyright
© 2017. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.